Pharm Test 3 Flashcards
Distribution depends on: 5 things
BF, capillary permeability, protein binding, lipophilicity, tissue volume
Plasma Compartment
(intravascular fluid), low Vd, 4% water weight, high mol weight drugs
Extracellular Compartment
(interstitial and plasma), high Vd, 20% water weight, low mol weight drugs
Volume of Distribution (eq)
Vd= dose [ ] / plasma drug [ ] (or total fluid drug [ ])
Half life determines
dose frequency, elimination, length of effect
Clearance (eq)
CL= (.639 x Vd)/half life
First Order Kinetics
constant proportion
- rate of drug elimination is proportional to drug [ ]
Zero Order Kinetics
constant rate
-rate of elimination is independent to drug [ ]
Biotranformations Phases 1 and 2
- Goal is to become hydrophilic for excretion
phase 1= adds polarized group (hydrolysis, oxidation by CYP 450 enzyme)
phase 2= links to acid= inactive (conjugation)
Urine Excreion=
filtration + secretion - reabsorption
Steady State proportional to? and inversely to?
- infusion
- clearance
Loading Dose (eq)
LD= Vd x Css (mg)
Maintenance Dose (eq)
MD= CL x Css (mg/kg/hr)
Drug Approval Process (4 steps)
in vitro, animal testing, clinical testing, marketing
Clinical Trials (4 phases)
- phase 1= small population, evaluate dose response
- phase 2= evaluates efficacy, larger group, placebo, blind
- phase 3= lots of population, comparison with other drugs, evaluate effects, placebo, blind
- phase 4= post marketing surveillance, toxicity
Drug must have appropriate
size, electrical charge, shape, atomic composition
Drug Electrical Charge (receptor bonds) - 3
- covalent= irreversible
- electrostatic= pos attract to neg
- hydrophobic= weak (more selective)
Major Receptor Families
- ligand gated ion channels (sec)
- g protein/cascade (min)
- enzyme linked receptors: activates enzyme (hours)
- intracellular receptors (days)= makes protein
Spare Receptors
only a fraction of total receptors needed to elicit max response
Protection from Excess Stimulation (3)
- desensitization
- down regulation
- refractory period
Potency vs Efficacy
P= amount of drug needed to produce given percent effect E= magnitude of response a drug causes
EC50
concentration producing 50% of max effect (potency)
4 Laws of Drug Receptor
1- drug and receptor combine reversibly
2- occupied receptors proportional to # of drug and receptors
3- magnitude proportional to activated receptors
4- plateau effect because of limited # of receptors
Agonist
Binds to receptor and makes response
1- full agonist- produce Emax
2- partial agonist- can’t produce Emax
3- inverse agonist- stabilized inactive form
Antagonist
blocks response
1- competitive- enough agonist can overcome it (high potency)
2- noncompetitive- cannot be overcome by agonist (lower Emax)
a- irreversible- covalent bond can’t come off
b- allosteric- binds to different site and blocks activation
3- functional- different receptor and opposite effect
4- chemical- drug binds to agonist
Quantal Dose-Response (ED50 and TD50)
measure safety
- ED50- dose for therapeutic effect in 50% population
- TD50- dose for toxic effect in 50% population
Therapeutic Index (eq)
TI= (TD50)/(ED50)
needs to be above 2
